复旦大学邵志敏研究组近日取得一项新成果。经过不懈努力，他们的最新研究提出了抗体驱动药物结合物SHR-A1811新辅助治疗HER2-阳性乳腺癌症疗效的空间决定因素。这一研究成果于2025年4月10日发表在国际顶尖学术期刊《癌细胞》上。

研究人员进行了一项预先指定的转化研究，以确定SHR-A1811治疗的HER2阳性乳腺癌患者的治疗生物标志物，这些患者来自2期新辅助FASCINATE-N试验，主题是DNA和RNA测序，计算病理学和单细胞原位空间成像。在激素受体（HR）阴性亚组中，更高比例和更多的免疫细胞（即肿瘤浸润淋巴细胞[TILs]）浸润，特别是细胞毒性T细胞，与更好的治疗反应相关。在HR阳性亚组中，HER2强阳性肿瘤细胞的紧密性和聚集性，而不是均匀分布，与较低的反应率和HER2发光样（HER2-LUM）亚型——更接近于HR+/HER2乳腺癌。此外，课题组研究人员开发了一种临床实用的预测模型，能够根据临床病理特征和病理图像预测SHR-A1811和其他新型ADC的新辅助治疗反应。

据介绍，选择下一代抗人表皮生长因子受体2 （HER2）抗体-药物偶联物（ADCs）的最佳候选物仍然具有挑战性。

附：英文原文

Title: Spatial determinants of antibody-drug conjugate SHR-A1811 efficacy in neoadjuvant treatment for HER2-positive breast cancer

Author: Ding Ma, Lei-Jie Dai, Xiang-Rong Wu, Cheng-Lin Liu, Shen Zhao, Hang Zhang, Li Chen, Yi Xiao, Ming Li, Yi-Zhi Zhao, Lin Yang, Tong Zhou, Jun-Jie Li, Wen-Tao Yang, Yi-Zhou Jiang, Zhi-Ming Shao

Issue&Volume: 2025-04-10

Abstract: Selecting optimal candidates for next-generation anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugates (ADCs) remains challenging. We conduct a prespecified translational study to identify treatment biomarkers in SHR-A1811-treated HER2-positive breast cancer patients from the phase 2 neoadjuvant FASCINATE-N trial using DNA and RNA sequencing, computational pathology, and single-cell in situ spatial imaging. In the hormone receptor (HR)-negative subgroup, a higher proportion and more infiltration of immune cells (i.e., tumor-infiltrating lymphocytes [TILs]), particularly cytotoxic T cells, are associated with better treatment responses. In the HR-positive subgroup, the closeness and aggregation of HER2-strong-positive tumor cells, as opposed to a uniform distribution, are linked to a lower response rate and HER2 luminal-like (HER2-LUM) subtype, which more closely resembles HR+/HER2 breast cancer. In addition, we develop a clinically practical predictive model capable of predicting neoadjuvant treatment responses to SHR-A1811 and other novel ADCs based on clinicopathological characteristics and pathological images.

DOI: 10.1016/j.ccell.2025.03.017

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00118-7